Dendritic cell activation, phagocytosis and CD69 expression on cognate T cells are suppressed by n-3 long-chain polyunsaturated fatty acids

Authors

  • Heather Teague,

    1. Department of Biochemistry and Molecular Biology, East Carolina University, Greenville, NC, USA
    2. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
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  • Benjamin Drew Rockett,

    1. Department of Biochemistry and Molecular Biology, East Carolina University, Greenville, NC, USA
    2. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
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  • Mitchel Harris,

    1. Department of Biochemistry and Molecular Biology, East Carolina University, Greenville, NC, USA
    2. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
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  • David A. Brown,

    1. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
    2. Department of Physiology, East Carolina University, Greenville, NC, USA
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  • Saame Raza Shaikh

    Corresponding author
    1. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
    • Department of Biochemistry and Molecular Biology, East Carolina University, Greenville, NC, USA
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Correspondence: Dr Saame Raza Shaikh, East Carolina University, Greenville, NC 27834, USA. Email: shaikhsa@ecu.edu

Senior author: Dr. Saame Raza Shaikh

Abstract

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are bioactive n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in fish oil that exert immunosuppressive effects. A significant amount of literature shows that n-3 LCPUFAs suppress dendritic cell (DC) function in vitro; however, few studies have determined if the effects are emulated at the animal level. In this study, we first focused on the functional consequences of 5% (weight/weight) fish oil on splenic CD11c+ DCs. Administration of n-3 LCPUFAs, modelling human pharmacological intake (2% of total kcal from EPA,1·3% from DHA), to C57BL/6 mice for 3 weeks reduced DC surface expression of CD80 by 14% and tumour necrosis factor-α secretion by 29% upon lipopolysaccharide stimulation relative to a control diet. The n-3 LCPUFAs also significantly decreased CD11c+ surface expression and phagocytosis by 12% compared with the control diet. Antigen presentation studies revealed a 22% decrease in CD69 surface expression on transgenic CD4+ T lymphocytes activated by DCs from mice fed fish oil. We then determined if the functional changes were mechanistically associated with changes in lipid microdomain clustering or plasma membrane microviscosity with n-3 LCPUFAs, as reported for B and T lymphocytes. Fish oil administration to mice did not influence cholera-toxin induced lipid microdomain clustering or microviscosity, even though EPA and DHA levels were significantly elevated relative to the control diet. Overall, our data show that n-3 LCPUFAs exert immunosuppressive effects on DCs, validating in vitro studies. The results also show that DC microdomain clustering and microviscosity were not changed by the n-3 LCPUFA intervention used in this study.

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